ARE ATP-SENSITIVE POTASSIUM CHANNELS INVOLVED IN THE PRONOUNCED ANTIARRHYTHMIC EFFECTS OF PRECONDITIONING

Objective: The aim was to determine whether the antiarrhythmic effects of preconditioning are modified by blockade of K+ATP channels with gl ibenclamide in a model (anaesthetised dogs) in which this procedure ha s previously been shown to prevent the effects of preconditioning in r educing myocardial infarct size. Methods: 10 mongrel dogs were precond itioned by two 5 min occlusions of the left anterior descending corona ry artery, separated by a 20 min reperfusion period, and then subjecte d, 20 min later, to a prolonged (25 min) occlusion and to subsequent r eperfusion. In another 10 dogs glibenclamide (300 mug.kg-1) was given by intravenous injection both after the first preconditioning stimulus and before the prolonged occlusion. Control dogs (25) were subjected to a 25 min occlusion followed by reperfusion; five of these dogs also received glibenclamide. Results: Preconditioning reduced the severity of ventricular arrhythmias, epicardial ST segment elevation, and the degree of inhomogeneity of conduction. The antiarrhythmic effect of pr econditioning was attenuated by glibenclamide (twice as many ventricul ar premature beats and more episodes of ventricular tachycardia) but t here was no modification of preconditioning induced reduction in ventr icular fibrillation either during ischaemia or during reperfusion, or on survival (0% in controls; 50% in preconditioned dogs with or withou t glibenclamide). Glibenclamide did, however, prevent the effects of p reconditioning on the inhomogeneity of conduction and, less markedly, on epicardial ST segment elevation. Conclusions: In a similar model to that in which it has previously been shown that glibenclamide prevent s the effect of preconditioning in reducing myocardial infarct size (s uggesting involvement of K+ATP channels), the most pronounced antiarrh ythmic effects of preconditioning (reduction in ventricular fibrillati on; increase in survival) were not modified by glibenclamide. This, an d other evidence, suggests that the mechanisms of the protective effec t of preconditioning in reducing the severity of arrhythmias and on in farct size are not the same.